Abstract
Background: Berberine (BBR) plays a neuroprotective role in the pathogenesis of Alzheimer’s disease (AD), inhibiting β-amyloid (Aβ) production and promoting Aβ clearance. Advanced glycation end products (AGEs) promote Aβ aggregation and tau hyperphosphorylation. The activation of mTOR signaling occurring at the early stage of AD has a prominent impact on the Aβ production. This work focused on whether BBR regulates the production and clearance of ribosylation-induced Aβ pathology via inhibiting mTOR signaling.Methods: Western Blot and Immunofluorescence staining were used to detect the related proteins of the mammalian target of Rapamycin(mTOR) signaling pathway and autophagy, as well as the related kinases of Aβ generation and clearance. Tissue sections and Immunofluorescence staining were used to observe Aβ1-42 in APP/PS1 mice hippocampal. Morris water maze (MWM) test was used to measure the spatial learning and memory of APP/PS1 mice.Results: BBR improves spatial learning and memory of APP/PS1 mice. BBR limits the activation of mTOR/p70S6K signaling pathway and enhances autophagy process. BBR reduces the activity of BACE1and γ-secretase induced by D-ribose, and enhances Aβ-degrading enzymes and Neprilysin, and inhibits the expression of Aβin APP/PS1 mice.Conclusions: BBR ameliorates ribosylation-induced Aβ pathology via inhibiting mTOR/p70S6K signaling, and improves spatial learning and memory of the APP/PS1 mice.
Dl‑3n‑butylphthalide improves spatial learning and memory in rats with vascular dementia by reducing autophagy via regulation of the mTOR signaling pathway
